Perivascular Neuropilin-1 expression is an independent marker of improved survival in renal cell carcinoma

Renal cell carcinoma (RCC) treatment has improved in the last decade with the introduction of drugs targeting tumor angiogenesis. However, the 5-year survival of metastatic disease is still only 10–15%. Here, we explored the prognostic significance of compartment-specific expression of Neuropilin 1 (NRP1), a co-receptor for vascular endothelial growth factor (VEGF). NRP1 expression was analyzed in RCC tumor vessels, in perivascular tumor cells, and generally in the tumor cell compartment. Moreover, complex formation between NRP1 and the main VEGF receptor, VEGFR2, was determined. Two RCC tissue microarrays were used; a discovery cohort consisting of 64 patients and a validation cohort of 314 patients. VEGFR2/NRP1 complex formation in cis (on the same cell) and trans (between cells) configurations was determined by in situ proximity ligation assay (PLA), and NRP1 protein expression in three compartments (endothelial cells, perivascular tumor cells, and general tumor cell expression) was determined by immunofluorescent staining. Expression of NRP1 in perivascular tumor cells was explored as a marker for RCC survival in the two RCC cohorts. Results were further validated using a publicly available gene expression dataset of clear cell RCC (ccRCC). We found that VEGFR2/NRP1 trans complexes were detected in 75% of the patient samples. The presence of trans VEGFR2/NRP1 complexes or perivascular NRP1 expression was associated with a reduced tumor vessel density and size. When exploring NRP1 as a biomarker for RCC prognosis, perivascular NRP1 and general tumor cell NRP1 protein expression correlated with improved survival in the two independent cohorts, and significant results were obtained also at the mRNA level using the publicly available ccRCC gene expression dataset. Only perivascular NRP1 expression remained significant in multivariable analysis. Our work shows that perivascular NRP1 expression is an independent marker of improved survival in RCC patients, and reduces tumor vascularization by forming complexes in trans with VEGFR2 in the tumor endothelium. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

成都市龙泉驿区2011-2015年手足口病流行特征分析

目的 对四川省成都市龙泉驿区2011-2015年手足口病流行特征进行分析,为今后制定和修改防控策略提供依据.方法 对龙泉驿区2011-2015年手足口病监测资料进行描述性统计分析及时间和空间扫描统计分析.结果 龙泉驿区5年间共报告手足口病病例9 067例,年平均发病率210.83/105;重症病例241例,占病例总数的2.66％,死亡2例.1-3岁散居儿童为该病的高发人群.4-7月和10-12月是发病的高峰月份.EV71是重症病例和死亡病例的主要病原体.聚集性疫情主要集中于幼托机构,市级幼儿园聚集性疫情发生最少.结论 2011-2015年龙泉驿区手足口病发病水平呈逐年增高趋势,应重点加强散居儿童的社区防控力度,落实幼托机构的防控措施.     

淄博市2013-2015年手足口病空间自相关分析

目的分析淄博市2013-2015年手足口病的空间分布特征及空间聚集性.方法运用空间自相关分析方法,以乡镇为空间单位对淄博市手足口病监测数据进行分析.结果2013-2015年,全局Moran's I系数分别为0.15(P＜0.001)、0.08(P=0.070)和0.30(P＜0.001).局域G统计量显示,2013年和2014年淄博市手足口病发病热点主要位于高青县,2015年发病热点主要位于周村区及其邻近乡镇.结论淄博市手足口病发病存在明显的空间聚集性,发病热点的探测有助于淄博市手足口病区域化防控策略的制定.     

基于GIS的南昌县血吸虫病疫情聚集区域综合探测研究

目的探测江西省南昌县血吸虫病疫情聚集区范围。方法收集2009年南昌县血吸虫病流行区血吸虫感染率数据,采用ArcGIS 9.2软件中空间聚集性分析、全局自相关以及空间热点探测方法,绘制空间自相关系数图,描述不同空间距离尺度下的血吸虫感染率自相关指数变化趋势;结合实际情况,以代表性的距离为空间关系参数,对研究区域的血吸虫感染率热点区域进行探测。结果2009年研究区域内的血吸虫感染空间分布具有明显的聚集性;从自相关系数图发现在空间距离尺度为1 900、2 600、3 800 m和5 000 m时出现了波峰;结合研究区域地理环境,发现在空间距离尺度为5 000 m的血吸虫病热点区域更符合实际,存在2个热点区域和2个次热点区域。结论空间聚集性分析结合空间自相关分析能够更加精确地探测血吸虫病疫情聚集区域。     

三峡工程对库区重庆段钉螺生长条件影响研究

目的了解三峡工程建成以后,库区气候、植被、淹没等条件变化对钉螺孳生的可能影响。方法利用ArcGIS软件的空间分析功能,结合气象资料及重点研究区1:1万和库区重庆段1:5万数字高程模型(DEM)就阶段性淹没区的气候条件、淹没时间、淹没区植被情况以及阶段性淹没可能对钉螺生长的影响进行综合分析。结果三峡库区淹没时间、气温、降水、日照时间、植被种类及覆盖度均适合钉螺,但其冬季蓄水、夏季放水的特点对钉螺的生长不利。结论三峡库区形成的"冬水夏陆"的洲滩环境不适于钉螺孳生,如能从源头上控制钉螺的外来输入问题,库区可避免成为钉螺孽生区。     

Proximity to major roadways is a risk factor for airway hyper-responsiveness in adults

BACKGROUND:

Proximity to major roads is reported to be associated with asthma and airway hyper-responsiveness in children. Similar studies using objective measurements in adults are not available in Canada.

OBJECTIVE:

To test the hypothesis that adult asthmatic patients who live close to major roads and highways in an urban environment are at a risk of moderate to severe airway hyper-responsiveness.

METHODS:

Airway responsiveness was determined using methacholine bronchial provocation (PC₂₀) tests in a cohort of 2625 patients who attended an outpatient clinic in Hamilton, Ontario. Patient addresses were geocoded in a geographic information system to determine proximity to major roads and highways. Multivariate linear and multinomial regression analyses were used to assess whether proximity to roads was a risk factor for airway hyper-responsiveness as measured by PC₂₀ methacholine.

RESULTS:

Patients who lived within 200 m of a major road had increased odds (OR 1.38 [95% CI 1.04 to 1.85]) of having moderate airway hyper-responsiveness (0.25 mg/mL 20 <2.0 mg/mL) compared with having a normal response (PC₂₀ >16 mg/mL). Spatial analysis also revealed that the majority of patients with severe airway hyper-responsiveness lived within the urban core of the city while those with moderate to mild hyper-responsiveness were also dispersed in rural areas.

CONCLUSIONS:

In an adult population of patients attending an outpatient respiratory clinic in Hamilton, living close to major roadways was associated with an increased risk of moderate airway hyper-responsiveness. This correlation suggests that exposure to traffic emissions may provoke the pathology of airway hyper-responsiveness leading to variable airflow obstruction.     

七氟醚对幼鼠获取空间学习记忆能力及海马pERK1/2表达的影响

目的探讨七氟醚对幼鼠获取空间学习记忆能力及海马p ERK1/2表达的影响。方法出生后14 d SD幼鼠54只,随机分为对照组(C组)、七氟醚5%组(Sevo组)、假手术组(Sham组)各18只。C组不做任何处理,Sevo组幼鼠暴露于5%的七氟醚4 h,Sham组幼鼠吸入氧气4 h,1周、3周、6周后于上午8:00~11:00应用Morris水迷宫对幼鼠进行7 d的行为学观察,记录逃避潜伏期,行为学结束后随即取出6只幼鼠用免疫组化法测定海马CA1区神经元p ERK1/2的表达。结果与Sham组比较,Sevo组逃避潜伏期和探索时间明显延长(P<0.01),Sevo组海马CA1区神经元p ERK1/2的表达明显减少(P<0.01);Sham组与C组逃避潜伏期时间差异无统计学意义,海马CA1区神经元p ERK1/2的表达之间差异无统计学意义。结论七氟醚对幼鼠获取空间学习记忆能力的影响与抑制海马p ERK1/2表达有关。     

基于地理信息系统的医疗设施空间分布研究

如何优化医疗设施空间分布,最大限度利用医疗卫生资源、保障医疗服务公平性和可及性是政府卫生管理部门经常遇到的难题。地理信息系统技术在医疗设施空间布局研究中得到广泛的应用。基于地理信息系统的医疗设施空间分布研究方法主要包括基于地理学空间相互作用理论的区位分析模型方法、基于运筹学规划技术的区位——配置模型方法和优势度模型方法。     

Stress Changes the Spatial Arrangement of Neurons and Glial Cells of Medial Prefrontal Cortex and Sertraline and Curcumin Prevent It

Objective

The present study explored the three-dimensional spatial arrangements of the neurons and glial cells within the medial prefrontal cortex (mPFC) of rats.

Methods

It evaluated the arrangement for differences after stress with or without treatment with curcumin and sertraline using second-order stereology. Orientator method was applied to obtain isotropic uniform random sections of mPFC. The pair correlation g(r) and cross-correlation functions were estimated by counting dipole probes superimposed on histological sections of mPFC.

Results

The mean total volume of neurons and glial cells was 0.80 (0.05) and 0.40 (0.07), respectively in the control group. The corresponding values decreased by 50% in the stressed group. The curve of g(r) for the neurons and glial cells showed a wider gap between the stressed rats'' mPFC. Theses indicate a negative correlation (repulsion) between the neurons and glial cells in the stressed rats. Evaluation of the cross-correlation function of the neurons and glial cells also showed a negative correlation in the stressed group. The estimated values of the global degree of order in the spatial point pattern for neurons and glial cells were 0.62 and 0.20 in control and stressed animals, respectively. Curcumin and sertraline protected the spatial arrangements of the cells after stress induction in rats. In addition, the volume of the neurons and glial cells remained unchanged after stress.

Conclusion

Dissociation of the neurons and glial cells can is seen at some places in the stressed rats'' cortex. However, the spatial arrangement of the cells was remained unchanged in curcumin+stress and sertraline+stress rats.     

From Gesture to Sign Language: Conventionalization of Classifier Constructions by Adult Hearing Learners of British Sign Language

There has long been interest in why languages are shaped the way they are, and in the relationship between sign language and gesture. In sign languages, entity classifiers are handshapes that encode how objects move, how they are located relative to one another, and how multiple objects of the same type are distributed in space. Previous studies have shown that hearing adults who are asked to use only manual gestures to describe how objects move in space will use gestures that bear some similarities to classifiers. We investigated how accurately hearing adults, who had been learning British Sign Language (BSL) for 1–3 years, produce and comprehend classifiers in (static) locative and distributive constructions. In a production task, learners of BSL knew that they could use their hands to represent objects, but they had difficulty choosing the same, conventionalized, handshapes as native signers. They were, however, highly accurate at encoding location and orientation information. Learners therefore show the same pattern found in sign-naïve gesturers. In contrast, handshape, orientation, and location were comprehended with equal (high) accuracy, and testing a group of sign-naïve adults showed that they too were able to understand classifiers with higher than chance accuracy. We conclude that adult learners of BSL bring their visuo-spatial knowledge and gestural abilities to the tasks of understanding and producing constructions that contain entity classifiers. We speculate that investigating the time course of adult sign language acquisition might shed light on how gesture became (and, indeed, becomes) conventionalized during the genesis of sign languages.